Ultrastructural localization of serotonin2A receptors in the middle layers of the rat prelimbic prefrontal cortex
Abstract
Cortical serotonin(2A) receptors are hypothesized to be involved in the pathology and treatment of schizophrenia. Light microscopic studies in the rat prefrontal cortex have localized serotonin(2A) receptors to the dendritic shafts of pyramidal and local circuit neurons. Electrophysiological studies have predicted that these receptors are also located on glutamate terminals, whereas neurochemical studies have hypothesized that they are located on dopamine terminals in this area. The present study sought to determine the ultrastructural localization of immunoperoxidase labeling for serotonin(2A) receptors in the middle layers of the prelimbic portion of the rat prefrontal cortex. Serotonin(2A) receptor immunoreactivity was observed in 325 identifiable structures. Of these, 73% were postsynaptic profiles that were composed of either dendritic shafts (58%) or dendritic spine heads and necks (42%). Twenty-four percent of the labeled profiles were presynaptic axons and varicosities; most of these had morphological features that were characteristic of monoamine axons: thin diameter, lack of myelination, occasional content of dense-cored vesicles, and infrequent formation of synapses in single sections. The remainder of the labeled profiles (4%) were glial processes. These findings suggest that serotonin(2A) receptor-mediated effects within the rat prelimbic prefrontal cortex are primarily postsynaptic in nature, affecting both the spines of pyramidal cells and the dendrites of pyramidal and local circuit neurons in this area. The results further suggest that serotonin acts presynaptically via this receptor subtype, most likely at receptors on monoamine fibers, and only rarely directly on glutamate axons.
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In rodents, the 5-HT2A receptor expression pattern has been confirmed using immunohistochemistry, light and electron microscope immunocytochemistry, in situ hybridization, receptor autoradiography, and transgenic mice expressing EGFP under control of the 5-HT2A receptor promoter.
“In rodents, this expression pattern has been confirmed using immunohistochemistry (203–206), light and electron microscope immunocytochemistry (203), in situ hybridization (207, 208), receptor autoradiography (209), and transgenic mice expressing EGFP under control of the 5-HT2A receptor promoter (210).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [206]
The 5-HT2A receptor is expressed on dendritic shafts and dendritic spines of cortical neurons in both rodents and primates.
“The 5-HT 2A R, a common target of psychedelics, is expressed on dendritic shafts and dendritic spines of cortical neurons in both rodents and primates (Jakab and Goldman-Rakic, 1998;Miner et al., 2003;Jones et al., 2009;Weber and Andrade, 2010;Yoshida et al., 2011).”
From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Miner et al., 2003
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“The 5-HT2AR, a common target of psychedelics, is expressed on dendritic shafts and dendritic spines of cortical neurons in both rodents and primates (Jakab and Goldman-Rakic, 1998; Miner et al., 2003; Jones et al., 2009; Weber and Andrade, 2010; Yoshida et al., 2011).”
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- Authors
- Miner, L. A. H., Backstrom, J. R., Sanders-Bush, E., & Sesack, S. R.
- Affiliations
- University of Pittsburgh (US)
- Vanderbilt University (US)
- Corresponding author
- Sesack, S.R.
- ORCID
- Sesack, S.R.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 116
- Issue
- 1
- Pages
- 107-117
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1981875451
- Cited by
- 216
- References
- 1
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 9 · 2020: 7 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 5 · 2015: 8 · 2014: 8 · 2013: 12 · 2012: 7
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 50314, MH34007)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- prelimbic cortex, postsynaptic localization, presynaptic localization, dendritic spines, pyramidal neurons, local circuit neurons, schizophrenia, serotonin
- MeSH terms
- Animals, Dendrites, Dopamine, Immunoenzyme Techniques, Male, Microscopy, Electron, Receptors, Serotonin, Rats, Sprague-Dawley, Prefrontal Cortex, Presynaptic Terminals, Pyramidal Cells, Glutamic Acid, Receptor, Serotonin, 5-HT2A, Rats
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